ROLE OF EPIDERMAL GROWTH-FACTOR, PROSTAGLANDIN, AND SULFHYDRYLS IN STRESS-INDUCED GASTRIC-LESIONS
ROLE OF EPIDERMAL GROWTH-FACTOR, PROSTAGLANDIN, AND SULFHYDRYLS IN STRESS-INDUCED GASTRIC-LESIONS
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DOI：
10.1016/0016-5085(90)90464-c
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发表时间：
1990-12-01
期刊：
影响因子：
29.4
通讯作者：
DEMBINSKI, A
中科院分区：
文献类型：
--
作者：
KONTUREK, PK;BRZOZOWSKI, T;DEMBINSKI, A
表皮生长因子可促进胃黏膜生长，保护胃粘膜免受包括应激在内的各种溃疡的侵袭，但对其在应激性溃疡发病机制中的作用知之甚少。在本研究中，将完整和切除唾液腺的Wistar大鼠暴露于水浸泡和束缚应激中。在浸水束缚应激2-14小时内，胃溃疡形成逐渐增加，并伴随着胃粘膜DNA合成的减少。涎腺切除后，观察到应激性溃疡的数量显著增加，DNA合成进一步减少。外源性表皮生长因子和二甲基前列腺素E2显著减少了唾液腺完整的应激大鼠的溃疡，但这种减少在涎腺切除后明显减少。浸水束缚应激可使粘膜前列腺素E_2的生成量减少约50%，而抑制前列腺素E_2约90%的吲哚美辛预处理可使应激性溃疡的数量增加近一倍，并取消外源性表皮生长因子(但不包括二甲基前列腺素E_2)对应激性损伤的胃保护作用。二氟甲基鸟氨酸对鸟氨酸脱羧酶活性的抑制也增强了应激诱导的溃疡形成，并取消了表皮生长因子的保护作用，而精胺的应用几乎完全阻止了没有和有二氟甲基鸟氨酸预处理的大鼠的应激性溃疡。浸水束缚应激也显著降低了粘膜谷胱甘肽的含量。半胱胺增加组织谷胱甘肽，减少应激性溃疡，但N-乙基马来酰亚胺，一种巯基阻滞剂，减少粘膜谷胱甘肽的含量，而不影响应激性溃疡。这项研究表明，应激性溃疡伴随着粘膜DNA、前列腺素和谷胱甘肽合成的减少，唾液腺的存在可能通过释放表皮生长因子来减轻应激性溃疡的发生，表皮生长因子的部分作用是通过促进鸟氨酸脱羧酶活性、粘膜生长以及前列腺素和谷胱甘肽的形成。
Epidermal growth factor promotes the growth of and protects gastric mucosa against various ulcerogens, including stress, but little is known about its role in the pathogenesis of stress ulcerations. In this study, Wistar rats with intact and resected salivary glands were exposed to water-immersion and restraint stress. During 2-14 hours of water-immersion restraint stress, the formation of gastric ulcerations increased progressively and the duration of stress was accompanied by a decrease in DNA synthesis in the gastric mucosa. Following sialoadenectomy, a significant increase in the number of stress ulcerations and further reduction in DNA synthesis were observed. Exogenous epidermal growth factor and dimethyl prostaglandin E2 significantly reduced the ulcerations in the stressed rats with intact salivary glands, but this reduction was significantly less pronounced after sialoadenectomy. Water-immersion restraint stress also resulted in about 50% reduction in mucosal prostaglandin E2 generation, and the pretreatment with indomethacin, which suppressed prostaglandin E2 by about 90%, almost doubled the number of stress ulcerations and abolished the gastro-protective effect of exogenous epidermal growth factor (but not dimethyl prostaglandin E2) against the stress lesions. An inhibition of ornithine decarboxylase activity by difluoromethyl ornithine also augmented stress-induced ulcerogenesis and abolished the protective action of epidermal growth factor while the administration of spermine almost completely prevented stress ulcerations in rats both without and with pretreatment with difluoromethylornithine. Water-immersion restraint stress also significantly reduced mucosal content of glutathione. Cysteamine increased tissue glutathione and reduced stress ulcerations but N-ethylmaleimide, an sulfhydryl blocker, decreased mucosal content of glutathione without affecting the stress ulcerations. This study indicates that the stress ulcers are accompanied by the reduction in mucosal synthesis of DNA, prostaglandin, and glutathione and that the presence of salivary glands attenuates the stress ulcerogenesis probably by releasing epidermal growth factor which acts, in part, by enhancing ornithine decarboxylase activity, mucosal growth, and prostaglandin and glutathione formation.